Validation of a PD-1/CD28 chimeric switch receptor to augment CAR-T function in dogs with spontaneous B-cell lymphoma.

This is the authors' abstract. We don't add key points for this paper.

Chimeric antigen receptor (CAR) T cell therapy has achieved unprecedented clinical outcomes in patients with relapsed/refractory B cell leukemias; however, response rates in patients with large B cell lymphoma (LBCL) are less impressive. Expression of PD-1 on activated T cells and PD-L1 on malignant, stromal, and immune cells within the tumor microenvironment (TME) contribute to CAR-T exhaustion, hypofunction, and treatment failures. Here, a comparative approach is taken to develop a chimeric switch receptor (CSR) with potential to augment CAR-T persistence, function, and clinical efficacy in immune competent, pet dogs with spontaneous B cell lymphoma (BCL). We show that similar to human CAR-T cells, expression of a PD-1/CD28 CSR in canine CAR-T cells results in enhanced function against PD-L1